The present invention relates generally to identification of unknown members of a sample by mobility characteristics, and more particularly to devices that analyze compounds via high field asymmetric waveform ion mobility spectrometry.
There are a number of different circumstances in which it is desirable to perform a chemical analysis to identify compounds in a sample. Such samples may be taken directly from the environment or they may be provided by front end specialized devices to separate or prepare compounds before analysis. Unfortunately, recent events have seen members of the general public exposed to dangerous chemical compounds in situations where previously no thought was given to such exposure. There exists, therefore, a demand for low cost, accurate, easy to use, and reliable devices capable of detecting the chemical makeup of a sample.
One class of known chemical analysis instruments are mass spectrometers. Mass spectrometers are generally recognized as being the most accurate type of detectors for compound identification, given that they can generate a fingerprint pattern for even fragment ions. However, mass spectrometers are quite expensive, easily exceeding a cost of $100,000 or more and are physically large enough to become difficult to deploy everywhere the public might be exposed to dangerous chemicals. Mass spectrometers also suffer from other shortcomings such as the need to operate at relatively low pressures, resulting in complex support systems. They also need a highly trained operator to tend to and interpret the results. Accordingly, mass spectrometers are generally difficult to use outside of laboratories.
A class of chemical analysis instruments more suitable for field operation is known as are known as Field Asymmetric Ion Mobility Spectrometers (FAIMS), also known as Radio Frequency Ion Mobility Spectrometers (RFIMS), and Differential Mobility Spectrometers (DMS), among other names. This type of spectrometer subjects an ionized gas sample to a varying high-low asymmetric electric field and filters ions based on their field mobility.
The gas sample flows through a field which allows only selected ion species to pass through, according to the compensation voltage, and specifically only those ions that exhibit particular mobility responses to the field. An ion detector then collects detection intensity data for the detected ions. The intensity data exhibit attributes such as “peaks.” These peaks are interpreted according to the compensation voltage at which a species of ion is able to pass through an asymmetric field of set field parameters.
A typical FAIMS device includes a pair of electrodes in a drift tube. An asymmetric field is applied to the electrodes across the ion flow path. The asymmetric RF field, as shown in FIG. 1A, alternates between a high or “peak” field strength and a low field strength. The field varies with a particular time period, t, (frequency) and duty cycle d. Field strength, E, varies as the applied voltage V and size of the gap between electrodes. Ions will pass through the gap between the electrodes only when their net transverse displacement per period of the asymmetric field is zero; in contrast, ions that undergo a net displacement will eventually undergo collisional neutralization on one of the electrodes. In a given Radio Frequency (RF) asymmetric field, a displaced ion can be restored to the center of the gap (i.e. compensated, with no net displacement for that ion) when a low strength DC electric field (the compensation voltage, Vcomp) is superimposed on the RF. Ions with differing displacement (owing to characteristic dependence of mobility in the high field condition) can be passed through the gap at compensation voltages characteristic of a particular ion and this is accomplished by applying various strengths of Vcomp. In this case, this system can function as continuous ion filter; or a scan of Vcomp will allow complete measure of ion species in the analyzer. The recorded image of the spectral scan of the sample is sometimes referred to as a “mobility scan” or as an “ionogram”).
Examples of mobility scans based on the output from a FAIMS device are shown in FIGS. 1B-1 and 1B-2. The compounds analyzed here consisted of acetone and an isomer of xylene (o-xylene). In the first case (FIG. 1B-1) a single compound, acetone, was independently applied to the FAIMS analyzer. The illustrated plot is typical of the observed response of the FAIMS device, with an intensity of detected ions dependent on the compensation voltage (Vcomp). For example, the acetone sample exhibited a peak intensity response at a compensation voltage of approximately −2 volts.
FIG. 1B-2 illustrates the results when analyzing a mixture of the two compounds, here, acetone and o-xylene. The combined response shows two peaks in approximately the same region as for the independent case. The compounds in the mixture can therefore be detected by comparing the response against the library, for example, of stored known responses for independently analyzed compounds, or libraries of mixtures. Thus, the independently analyzed compounds shown in FIG. 1B-1 can be stored in a computer system, and when compound responses such as that in FIG. 1B-2 are observed, the relative locations of the peaks can be compared against the stored responses in the library to determine the constitution of the mixture.
A problem occurs, however, especially with FAIMS devices, in that relatively complex samples can be very difficult to detect. First of all, the peaks as seen in the typical FAIMS spectra are generally broad in width. Therefore, compounds having similar peak compensation voltages may therefore be difficult to separate from one another. Indeed, there may be particular conditions where two different chemicals actually exhibit the same compensation voltage at a given maximum intensity for the applied asymmetric RF voltage (referred to here as peak RF voltage). In such a case, it is not possible to resolve between two different chemicals at all. Another problem may occur when two or more chemical species have the same or almost the same mobility. This is most likely to happen in the low electric field regime where most existing ion mobility spectrometer systems operate. Therefore, if two or more chemical species have the same or almost the same mobility, then their spectroscopic peaks will overlap, and identification and quantification of individual species will be difficult or impossible.
A specific RF level and compensation voltage will permit only a particular species of ion (according to mobility) to pass through the filter to the detector. By noting the RF level and compensation voltage and the corresponding detected signal, various ion species can be identified, as well as their relative concentrations (as seen in the peak characteristics).
Consider a plot of mobility dependence on electric field, as shown in FIG. 1C. This figure mobility versus electric field strength for three examples of ions, with field dependent mobility (expressed as the coefficient of high field mobility, a) shown for species at greater, equal to and less than zero. The velocity of an ion can be measured in an electric field, E, low enough so that velocity, V, is proportional to the electrical field as V=KE through a coefficient, K, called the coefficient of mobility. K can be shown to be theoretically related to the ion species and gas molecular interaction properties. This coefficient of mobility is considered to be a unique parameter that enables the identification of different ion species and is determined by, ion properties such as charge, size, and mass as well as the collision frequency and energy obtained by ions between collisions.
When the ratio of E/N is small, K is constant in value, but at increasing E/N values, the coefficient of mobility begins to vary. The effect of the electric field can be expressed approximately asK(E)=K(0)[1+α(E)]where K(0) is a low voltage coefficient of mobility, and α is a specific parameter showing the electric field dependence of mobility for a specific ion.
Thus, as exhibited in FIG. 1C, at relatively low electric field strengths, of say less than approximately 8,000 volts per centimeter (V/cm), multiple ions may have the same mobility. However, as the electric field strengths increase, the different species diverge in their response such that their mobility varies as a function of the applied electric field. This is a clear expression of the fact that ion mobility is independent of applied electric field at relatively low field strengths but is field-dependent at higher applied field strengths.
FIG. 1B demonstrates that each species can have a unique behavior in high fields according to its mobility characteristics. The ions passing through the filter are detected downstream. The detection signal intensity can be plotted, resulting in display of a characteristic detection peak for a given RF and Vcomp. Peak intensity, location, and shape are typically used for species identification.
However, a problem occurs, especially with FAIMS devices, in that relatively complex samples can be very difficult to discriminate. First of all, the peaks as seen in the typical FAIMS spectra are generally broad in width. Therefore, compounds having similar peak compensation voltages may be difficult to separate from one another. Indeed, there may be particular conditions where two different chemicals actually exhibit the same peak at the same compensation voltage at a given asymmetric RF field.
For example in FIG. 1D, there are four compounds each with a unique characteristic mobility curve that expresses the mobility dependence associated with that compound at each of various peak RF values and compensation voltage levels. Four different chemical compounds are shown, including lutidine, cyclohexane, benzene, and a chemical agent simulant dimethyl-methyl-phosphonate (DMMP). Each curve shows detection peaks at the various field conditions that in total are characteristic for the compound. As shown, there is a region 100 in which the mobility curves for DMMP and cyclohexane overlap with one another. Therefore, operating in a peak RF voltage region of from approximately 2,500 to 2,650 volts, at around −6 to −8 volts compensation, one would find it impossible to discriminate between the two compounds upon a single scan. In other words, the conventional spectral scan would plot the overlapping peaks as a single peak at that field condition.
A cylindrical FAIMS device is described in U.S. Pat. No. 5,420,424, where the amplitude of the asymmetric periodic potential is in the range of about 1 to 6 Kv or 2 to 5 Kv, and preferably at about 3 Kv, depending on the ionic species of interest. After the magnitude of the asymmetric voltage has been set, the compensation voltage is held constant or scanned to provide separation of the ionic species.
Even with these improvements, ion species detection is not error free, especially with complex sample mixtures. False negatives are dangerous, and false positives can be expensive and reduce trust in the device. This can be very serious where harmful compounds are being monitored. It is also desirable to have a fast and simple apparatus to achieve such detections with improved accuracy.